Amyotrophic lateral sclerosis - what it is and how to treat it. Treatment of amyotrophic lateral sclerosis

The first to describe and identify amyotrophic sclerosis as a separate nosology was a French psychiatrist Jean-Martin Charcot in 1869

ALS is like no other pathology. nervous system, has many synonyms for its name. This includes motor neuron disease or motor neuron disease, Charcot's disease, and Lou Gehrig's disease (the term is more often used in Western European countries and America). But no matter what this disease is called, it steadily leads to severe disability and inevitable death.

What is ALS?

(amyotrophic lateral sclerosis, ALS) is a chronic neurodegenerative constantly progressive pathology of the nervous system, characterized by damage to central and peripheral motor neurons, with the subsequent development of plegia (paralysis), muscle atrophy, bulbar and pseudobulbar disorders.

Amyotrophic lateral sclerosis in 95% of cases is a sporadic disease, that is, it has no direct connection with diseases of immediate relatives. 5% of diagnosed ALS is due to hereditary pathology. Familial ALS was first identified and confirmed on the island of Guam (Mariama Islands).

Motor neuron disease is quite rare - 1.5 - 5 cases per 100 thousand population. The peak incidence occurs at the age of about 50 years for the familial form of the disease and 60–65 years for the sporadic form. But this does not mean that Charcot's disease does not occur at a young age. Men suffer from ALS almost 1.5 times more often than women. Although, upon reaching 60 years of age, this difference disappears - representatives of both sexes get sick equally often.

ALS disease must be clearly differentiated from such a disease as amyotrophic lateral syndrome (ALS syndrome), because the latter is a manifestation of other diseases of the nervous system (for example, tick-borne encephalitis, stroke, etc.), and not a separate nosology. And most often these are curable diseases, which, when timely diagnosis and treatment do not lead to death.

Death with amyotrophic lateral sclerosis occurs as a result of complications such as congestive pneumonia, septic phenomena, failure of the respiratory muscles, etc.

A little terminology

To understand the essence of this terrible disease you need to understand a little about such complex neurological terminology as central and peripheral motor neuron, bulbar and pseudobulbar syndromes. Since these words will not mean anything to a person far from medicine.

The central motor neuron is located in the precentral gyrus of the cortex cerebral hemispheres, the so-called motor area. If damage to this part of the brain occurs, central (spastic) paralysis develops, which is accompanied by the following symptoms:

• muscle weakness of varying degrees of severity (from complete lack of movement to slight awkwardness of movements);
• increased muscle tone, development of spasticity;
• strengthening of tendon and periosteal reflexes;
• the appearance of pathological foot signs (Babinsky’s symptom, Rossolimo’s, Openheim’s, etc.).

Peripheral motor neurons are localized in the nuclei cranial nerves, in thickenings of the spinal cord at the cervical, thoracic and lumbosacral levels in its anterior horns. That is, in any case, below the cortical motor neurons. If these nerve cells Symptoms of peripheral (flaccid) paralysis occur:

• weakness in the muscles innervated by this group of cells;
• decreased tendon and periosteal reflexes;
• the appearance of muscle hypotonia;
• development of atrophic changes in muscles, due to their denervation;
• there are no pathological symptoms.

In ALS, damage occurs as peripheral, so central motor neurons, which causes the appearance of signs of central and peripheral paralysis in this pathology.

Bulbar palsy that develops in Lou Gehrig's disease occurs due to the degeneration of neurons located in the nuclei of the IX, X, XII pairs of cranial nerves. These structures are located in the brain stem, namely in medulla oblongata(from Latin bulbus). This syndrome manifests itself as weakness in the muscles of the pharynx, larynx, tongue and soft palate. Here are its main symptoms:

• dysarthria (impaired articulation due to weakness and atrophy of the tongue muscles);
• dysphonia (impaired voice formation) and nasolalia (nasal tone of voice);
• dysphagia (swallowing disorder);
• sagging of the soft palate and displacement of the uvula to the healthy side;
• loss (absence) of the pharyngeal reflex;
• drooling (occurs as a result of impaired swallowing);
• fibrillary twitching in the tongue (detected as small muscle contractions, fluttering).

Pseudobulbar palsy, which includes almost all of these symptoms, develops due to a bilateral violation of the structure of the corticobulbar tracts (that is, the nerve fibers connecting the cerebral cortex with the bulbar group of cranial nerve nuclei). Distinctive feature this syndrome is:

• preservation of the pharyngeal reflex;
• absence of atrophy and fibrillation in the tongue;
• increased mandibular reflex;
• the appearance of pathological reflexes of oral automatism (they are considered normal for childhood - proboscis, sucking, etc.);
• violent (involuntary) crying and laughter.

Considering that with amyotrophic lateral sclerosis, degeneration of both upper (central) and lower (peripheral) motor neurons occurs, bulbar palsy is very often combined with pseudobulbar palsy. In some forms of ALS, these syndromes may be the only manifestation of the disease; the rest simply do not have time to develop, since the symptoms of respiratory failure increase very quickly.

What are the causes and mechanisms of development of the disease?

The reliable reasons for the development of the sporadic form of Charcot's disease have not yet been established. Many researchers believe that “slow” factors provoke the development of ALS. infections: enteroviruses, ECHO virus, Coxsackie virus, retroviruses, HIV.

The virus destroys normal DNA structure of motor neurons, provoking the acceleration of their death (apoptosis). This is accompanied by the development of excitotoxicity - an excess of glutamate leads to overexcitation and death of motor neurons. The remaining cells may spontaneously depolarize, which is clinically manifested by fibrillations and fasciculations.

There is also a pathological effect on neurons autoimmune reactions(IgG disrupts the functioning of L-type calcium channels), changes in normal aerobic metabolism in them, an increase in the transmembrane current of sodium and calcium ions into cells, disruption of the activity of cell wall enzymes and destruction of its structural proteins and lipids.

At Johns Hopkins University in Baltimore, four-stranded DNA and RNA were identified in the motor neurons of ALS patients. This led to the appearance of the ubiquitin protein in the cytoplasm of neurons, or rather its aggregates, which are normally located in the nucleus. This change also accelerates neurodegeneration in amyotrophic lateral sclerosis.

Hereditary (familial) ALS is associated with a mutation in the gene located on chromosome 21 and encoding superoxide mutase-1. The disease is transmitted in an autosomal dominant manner.

Pathomorphological examination reveals atrophy of the motor cortex (precentral gyri) of the cerebral hemispheres, anterior horns of the spinal cord and motor nuclei bulbar group of cranial nerves. In this case, the dead motor neurons are replaced by neuroglia. Not only the bodies of motor neurons are affected, but also their processes - demyelination is observed (that is, destruction of the normal myelin sheath of axons) pyramid paths in the brainstem and lateral cords of the spinal cord.

Amyotrophic lateral sclerosis: symptoms

Early symptoms of Lou Gehrig's disease in most cases are slowly increasing weakness in the arms or legs. In this case, the distal parts of the extremities – the feet and hands – are more affected. The patient cannot fasten buttons, tie shoelaces, starts to stumble, twists legs. Such awkwardness is accompanied by external exhaustion (weight loss) of the limbs.

Most often symptoms asymmetrical. With careful observation of the patient, it is possible to detect in the affected limbs fasciculations– muscle twitching, wave-like, slight fluttering.

Many patients in the initial stages of the disease experience problems associated with weakness of the neck muscles that support the head in vertical position. That's why head hangs constantly and patients need special devices to hold it.

The disease progresses steadily and gradually the pathological process covers increasingly large muscle masses. Against the background of the development of peripheral paralysis, symptoms of central paralysis are added:

• hypertonicity and spasticity in the muscles,
• tendon and periosteal reflexes increase,
• pathological foot and wrist reflexes occur.

Very slowly, patients with amyotrophic lateral sclerosis completely lose the ability to move and care for themselves.

Along with this, the patient notes difficulty swallowing, difficulty speaking, change in voice and other symptoms of bulbar palsy, which is usually combined with pseudobulbar palsy.

Gradually, the pathological process affects the respiratory muscles - the most important is the damage to the diaphragm. In this regard, the phenomenon arises paradoxical breathing: when inhaling, the stomach of patients suffering from ALS sinks, and when exhaling, on the contrary, it protrudes.

Oculomotor disorders(paresis of gaze, impaired movements of the eyeballs, etc.) if they occur, then only at the terminal stage of motor neuron disease. Changes in sensitivity are not typical for of this disease, although some patients complain of strange discomfort and pain.

Also, amyotrophic lateral sclerosis does not have any abnormalities pelvic organ functions. But at the end of the disease, incontinence or retention of urine and stool is possible.

Patients usually remain sane and with clear memory until the end of their days, which further darkens their condition. Therefore, severe depressive disorders often occur. Only in 10 - 11% of cases of familial ALS is dementia associated with diffuse atrophy of the frontal cortex.

What forms does motor neuron disease take?

The modern classification of amyotrophic lateral sclerosis distinguishes 4 main forms:

• high (cerebral);
• bulbar;
• cervicothoracic;
• lumbosacral.

This division is quite arbitrary, since over time, motor neurons are damaged at all levels. This is rather necessary to establish the prognosis of the disease.

High (cerebral) form

High (cerebral) form ALS develops in 2 - 3% of cases and is accompanied by damage to neurons in the motor cortex (precentral gyrus) of the frontal lobe. With this pathology, spastic tetraparesis occurs (that is, both arms and legs are affected), which are combined with pseudobulbar syndrome. Symptoms of neurodegenerative changes in peripheral motor neurons practically do not appear.

Bulbar form

Bulbar form, found in a quarter of all cases of ALS, is expressed in damage to the nuclei of the cranial nerves (IX, X, XII pairs) located in the brain stem. This form of the disease manifests itself bulbar palsy(dysphagia, dysphonia, dysarthria), which, as the pathology progresses, is combined with atrophy of the muscles of the limbs and fasciculations in them, and central paralysis. Often, bulbar disorders are accompanied by pseudobulbar syndrome (increased mandibular reflex, the occurrence of spontaneous forced laughter or crying, reflexes of oral automatism).

Cervicothoracic form

The most common (about 50% of cases) form of motor neuron disease is cervicothoracic. In which symptoms of peripheral paralysis first develop in the arms (muscle atrophy, decrease or loss of tendon and periosteal reflexes, decreased muscle tone) and spastic paralysis in the legs. Then, with an “increase” in the level of neuronal damage, symptoms of central plegia in the hands appear (development of spasticity, revitalization of reflexes, pathological phenomena of the hand).

Lumbosacral form

Lumbosacral form ALS occurs in 20 - 25% of cases and manifests as flaccid (peripheral) paralysis of the lower extremities. As the disease progresses, it spreads to the overlying muscle masses (torso, arms) and adds signs of spastic (central) paralysis - hypertonicity in the muscles, increased reflexes, and the appearance of pathological foot signs.

How is the diagnosis of amyotrophic lateral sclerosis confirmed?

Diagnosis of this rare pathology has great value, since there are a number of diseases that mimic amyotrophic lateral sclerosis, but many of them are curable. The most striking signs of Charcot's disease: damage to central and peripheral motor neurons - occur already in the terminal stages of the disease. Therefore, a reliable diagnosis of ALS is based on the exclusion of other pathologies of the nervous system.

In Europe and America, the El Escorian criteria for the diagnosis of ALS, developed by the International Federation of Neurologists, are used. These include:

• reliable clinical signs of damage to the central motor neuron;
• clinical, electroneuromyographic and pathomorphological signs of peripheral motor neuron neurodegeneration;
• steady progression and spread of symptoms within one or more areas of innervation, identified during dynamic monitoring of the patient.

It is also important to exclude other pathologies that can lead to the development of such symptoms.

So, to diagnose amyotrophic lateral sclerosis, the following examination methods are used:

• examination and interview of the patient(history of life and illness). When examining, pay attention to a combination of signs of peripheral and central paralysis, affecting at least two or three areas of the body (upper and lower extremities, bulbar muscles); simultaneous presence of symptoms of bulbar and pseudobulbar palsy; absence of pelvic and oculomotor disorders, visual and sensory impairments, intact intellectual and mnestic functions;
• clinical blood and urine test;
• blood chemistry(CPK, C-reactive protein, level of electrolytes in the blood, kidney tests, liver tests, etc.) – in ALS, an increase in CPK levels and liver test parameters is often observed;
• determination of the level of certain hormones in the blood(for example, hormones thyroid gland);
• study of the composition of cerebrospinal fluid (cerebrospinal fluid) – in some patients with ALS (25%) there is an increase in the protein content in the cerebrospinal fluid;
• needle electroneuromyography(ENMG) – in patients suffering from amyotrophic lateral sclerosis, a “picket fence rhythm” (rhythmic fibrillation potentials) is determined, signs of damage to the anterior horns of the spinal cord in the complete absence of conduction disturbances along nerve fibers;
• neuroimaging study - MRI the brain and spinal cord in such patients reveals atrophy of the precentral gyrus cortex, thinning of the lateral cords and a decrease in the size of the anterior horns of the spinal cord;
• biopsy of muscles and nerves followed by histological examination– reveals signs of atrophic and denervation changes;
• molecular genetic examination– justified in cases of suspected familial ALS – a mutation in chromosome 21 is determined.

It is necessary to perform a whole series of examinations to reliably exclude curable diseases. Since the approach to therapy and the outcome of the disease will be completely different.

The disease amyotrophic lateral sclerosis has symptoms that are quite severe and difficult to correct.

At the moment, there is only one drug in the world that can slow the progression of the disease and delay the onset of respiratory failure in patients with amyotrophic lateral sclerosis. This riluzole(rilutek), developed in 1995. The mechanism of its action is associated with the suppression of the release of the neurotransmitter glutamate from nerve endings. Thus, the rate of motor neuron degeneration is reduced. This therapy prolongs the life of patients by a maximum of three months.

This drug has not yet been registered in the CIS countries, although it has been used in Europe and America for a long time.

Since there is no way to influence the etiological factor in the development of the disease, patients need care and symptomatic treatment:

• in the early stages of the disease (before the development of spastic changes in the muscles) physiotherapy and massage;
• to move, patients use canes and special chairs equipped with buttons for ease of use;
• when the head hangs down, use a Shants collar, special rigid or semi-rigid holders;
• When the first signs of swallowing problems appear, it is advisable to change the consistency of food to puree and liquid. After each meal, sanitation of the oral cavity is necessary. When it is difficult to take liquid food, they switch to tube feeding (through a nasogastric tube) or apply a gastrostomy (a hole in the skin in the stomach area through which food immediately enters the gastrointestinal tract);
• for the development of cramps in the calf muscles (cramps), carbamazepine, baclofen, magne B6, verapamil, diazepam are used;
• when spasticity appears in the muscles, muscle relaxants are used - baclofen, tizalud, sirdalud, mydocalm;
• for severe salivation, atropine, hyoscine are used, and antidepressants (amitriptyline) are also effective;
• For persistent pain syndrome, depression and sleep disturbances, tricyclic antidepressants (amitriptyline) and serotonin reuptake inhibitors (fluoxetine, sertraline) are recommended. Also, this group of drugs slightly reduces the frequency of attacks of violent laughter or crying. Severe sleep disturbance requires the prescription of sleeping pills (zolpidem). If antidepressants and analgesics are ineffective for relief pain syndrome use narcotic analgesics (morphine, tramadol);
• in case of respiratory failure in the early stages, it is possible to use auxiliary portable systems for non-invasive ventilation of the lungs. In the terminal stage of the disease, patients need constant use stationary mechanical ventilation in the intensive care unit;
• sometimes neuroprotectors (gliatilin, cerebrolysin, ceraxon), antioxidants (mexipridol), vitamin E, B vitamins, L-carnitine (elcar), etc. are used to improve the nutrition of muscles and brain cells, but many experts believe that the use of such therapy is unjustified and does not improve the condition of patients;
• such patients also need special means communications – laptops have been developed that can be controlled using eye movements;
• The help of a psychologist is urgently needed for both the ALS patient and his family.

Update: December 2018

Amyotrophic lateral sclerosis, or Lou Gehrig's disease, is a rapidly progressive disease of the nervous system characterized by damage to motor neurons in the spinal cord, cortex, and brain stem. Also, the motor branches of cranial neurons (trigeminal, facial, glossopharyngeal) are involved in the pathological process.

Epidemiology of the disease

The disease is extremely rare, approximately 2-5 people per 100,000. It is believed that men over 50 years of age are more often affected. Lou Gehrig's disease makes no exceptions for anyone; it affects people of different social status and various professions (actors, senators, Nobel laureates, engineers, teachers). The most famous patient was world baseball champion Loi Gering, after whom the disease took its name.

In Russia, amyotrophic lateral sclerosis has become widespread. Currently, the number of sick people is approximately 15,000-20,000 in the population. Among the famous people of Russia who have this pathology, we can mention the composer Dmitry Shostakovich, the politician Yuri Gladkov, and the pop singer Vladimir Migulya.

Causes of amyotrophic lateral sclerosis

The disease is based on the accumulation of pathological insoluble protein in the motor cells of the nervous system, leading to their death. The cause of the disease is currently unknown, but many theories exist. The main theories include:

• Viral - this theory was popular in the 60-70s of the 20th century, but was never confirmed. Scientists in the USA and USSR conducted experiments on monkeys, injecting them with extracts of the spinal cord of sick people. Other researchers tried to prove participation in the formation of the disease.
• Hereditary - in 10% of cases the pathology is hereditary;
• Autoimmune - this theory is based on the discovery of specific antibodies that kill motor nerve cells. There are studies that prove the formation of such antibodies against the background of other severe diseases (for example, with lung cancer or Hodgkin's lymphoma);
• Genetic - 20% of patients have disorders of the genes encoding the very important enzyme Superoxide dismutase-1, which converts Superoxide, which is toxic to nerve cells, into oxygen;
• Neuronal - British scientists believe that glial elements, that is, cells that ensure the vital activity of neurons, are involved in the development of the disease. Studies have shown that if astrocytes, which remove glutamate from nerve endings, have insufficient function, the likelihood of developing Lou Gehrig's disease increases tenfold.

Classification of amyotrophic lateral sclerosis:

Symptoms of amyotrophic lateral sclerosis

Any form of the disease has the same onset: patients complain of increasing muscle weakness, a decrease in muscle mass and the appearance of fasciculations (muscle twitching).

Bulbar form of ALS characterized by symptoms of damage to the cranial nerves (9, 10 and 12 pairs):

• Those who are ill have deteriorated speech and pronunciation, and it becomes difficult to move their tongue.
• Over time, the act of swallowing is disrupted, the patient constantly chokes, and food can pour out through the nose.
• Patients feel an involuntary twitching of the tongue.
• The progression of ALS is accompanied by complete atrophy of the muscles of the face and neck; patients completely lack facial expressions, they cannot open their mouths or chew food.

Cervicothoracic variant The disease primarily affects the patient’s upper limbs, symmetrically on both sides:

• Initially, patients feel a deterioration in the functionality of their hands, it becomes harder to write, play musical instruments, and perform complex movements.
• At the same time, the arm muscles are very tense and tendon reflexes are increased.
• Over time, weakness spreads to the muscles of the forearm and shoulder, they atrophy. The upper limb resembles a hanging whip.

Lumbosacral form usually begins with a feeling of weakness in the lower extremities.

• Patients complain that it has become more difficult for them to do work while standing, walk long distances, and climb stairs.
• Over time, the foot begins to sag, the leg muscles atrophy, and patients cannot even stand on their feet.
• Pathological tendon reflexes (Babinsky) appear. Patients develop urinary and fecal incontinence.

Regardless of which variant predominates in patients at the beginning of the disease, the outcome is still the same. The disease progresses steadily, spreading to all muscles of the body, including the respiratory ones. When the respiratory muscles fail, the patient begins to need artificial ventilation and constant care.

In my practice, I observed two patients with ALS, a man and a woman. They were distinguished by their red hair color and relatively young age (up to 40 years). Outwardly, they were very similar: there was no hint of muscles, an amicable face, and their mouth was always slightly open.

Such patients die in most cases from concomitant diseases (pneumonia, sepsis). Even with proper care, they develop bedsores (see), hypostatic pneumonia. Realizing the severity of their illness, patients fall into depression, apathy, and cease to be interested in the outside world and their loved ones.

Over time, the patient's psyche undergoes strong changes. The patient I observed for a year was distinguished by his capriciousness, emotional lability, aggressiveness, and lack of restraint. Conducting intellectual tests showed a decrease in his thinking, mental abilities, memory, and attention.

Diagnosis of amyotrophic lateral sclerosis

The main diagnostic methods include:

• MRI of the spinal cord and brain– the method is quite informative; it reveals atrophy of the motor parts of the brain and degeneration of pyramidal structures;
• cerebrospinal puncture– usually reveals normal or increased content squirrel;
• neurophysiological examinations– electroneurography (ENG), electromyography (EMG) and transcranial magnetic stimulation (TCMS).
• molecular genetic analysis– studies of the gene encoding Superoxide dismutase-1;
• biochemical blood test– reveals a 5-10-fold increase in creatine phosphokinase (an enzyme formed during muscle breakdown), a slight increase in liver enzymes (ALT, AST), accumulation of waste in the blood (urea, creatinine).

What happens in ALS

Due to the fact that ALS has similar symptoms to other diseases, differential diagnosis is made:

• brain diseases: posterior fossa tumors, multiple system atrophy,
• muscle diseases: oculopharyngeal myodystrophy, Rossolimo-Steinert-Kurshman myotonia
• systemic diseases
• diseases of the spinal cord: lymphocytic leukemia or lymphoma, spinal cord tumors, spinal amyotrophy, syringomyelia, etc.
• peripheral nerve diseases: Personage-Turner syndrome, Isaacs neuromyotonia, multifocal motor neuropathy
• myasthenia gravis, Lambert-Eaton syndrome - diseases of the neuromuscular junction

Treatment of amyotrophic lateral sclerosis

Treatment of the disease is currently ineffective. Medicines and proper care for the patient only prolong life expectancy without ensuring a complete recovery. Symptomatic therapy includes:

• Riluzole (Rilutek)– a well-proven drug in the USA and Great Britain. Its mechanism of action is to block glutamate in the brain, thereby improving the functioning of Superoxide Dismutase-1.
• RNA interference is a very promising method of treating ALS, the creators of which were awarded the Nobel Prize in Medicine. The technique is based on blocking the synthesis of pathological protein in nerve cells and preventing their subsequent death.
• Stem cell transplantation– studies have shown that stem cell transplantation into the central nervous system prevents the death of nerve cells, restores neural connections, and improves the growth of nerve fibers.
• Muscle relaxants – eliminate muscle spasms and twitching (Baclofen, Sirdalud).
• Anabolics (Retabolil)– to increase muscle mass.
• Anticholinesterase drugs(Prozerin, Kalimin, Pyridostigmine) – prevent the rapid destruction of acetylcholine in neuromuscular synapses.
• B vitamins(Neurorubin, Neurovitan), vitamins A, E, C - these drugs improve the conduction of impulses along nerve fibers.
• Antibiotics wide range actions(3-4 generation cephalosporins, fluoroquinolones, carbopenems) – indicated for development infectious complications, sepsis.

Complex therapy necessarily includes feeding through a nasogastric tube, massage, exercise therapy with a doctor, and consultations with a psychologist.

Forecast

Sadly, the prognosis for amyotrophic lateral sclerosis is unfavorable. Patients die literally within a few months or years; the average life expectancy for patients is:

• only 7% live more than 5 years
• with bulbar debut - 3-5 years
• for lumbar - 2.5 years

A more favorable prognosis for hereditary cases of the disease associated with mutations in the superoxide dismutase-1 gene.

The situation in Russia is overshadowed by the fact that patients are not provided with proper care, as evidenced by the fact that Riluzote, a drug that slows the course of the disease, was not even registered in Russia until 2011, and only in the same year the disease itself was included in the list " rare." But in Moscow there are:

• Fund for helping patients with amyotrophic lateral sclerosis at the Marfo-Mariinsky Mercy Center
• G.N.Levitsky Charitable Foundation for ALS Patients

Finally, I would like to add about the Ice Bucket Challenge charity event that took place in July 2014. It was aimed at raising funds to support patients with amyotrophic lateral sclerosis and became quite widespread. The organizers managed to raise more than $40 million.

The essence of the action was that a person either doused himself with a bucket of ice water and captured it on video, or donated a certain amount of money to a charitable organization. The event became quite popular due to the participation of popular performers, actors and even politicians.

Lateral (lateral) amyotrophic sclerosis still has the name ALS disease. Other names for this disease are also known: motor neuron disease, Charcot's disease, Motor neuron disease, Lou Gehrig's disease. What it is? It is an incurable degenerative disease of the central nervous system that progresses slowly, but affects both the cerebral cortex and the spinal cord and cranial nerve nuclei. This results in motor neuron damage, paralysis and muscle atrophy.

As a result, death occurs from failure of the respiratory muscles or from respiratory tract infections. ALS syndrome can also be observed, but this is a completely different disease.

This disease was first described by Charcot in 1869.

Causes of ALS

The cause of ALS is a mutation of certain proteins (ubiquitin) with the appearance of intracellular aggregates. Familial forms of the disease are observed in 5% of cases. Basically, ALS disease affects people over the age of forty-sixty years, of whom no more than 10% are carriers of the hereditary form; scientists still cannot explain the remaining cases by the influence of any external influences - ecology, injuries, diseases and other factors.

Symptoms of the disease

Early symptoms of the disease are numbness and weakness in the limbs, as well as difficulty speaking, but such signs apply to a large number of diseases. This makes diagnosis very difficult until the final period, when the disease has already entered the stage of muscle atrophy.

The most famous ALS patient: Stephen Hawking loves black holes and TV

The initial lesions of ALS can occur on various parts of the body, with up to 75% of patients the disease begins in the extremities, mainly the lower ones. What it is? There is difficulty walking, the patient begins to stumble, and stiffness occurs in the ankle. When the upper extremities are affected, the flexibility of the fingers and strength in the hands are lost.

ALS may manifest itself (bulbar form), which in the next stage progresses to difficulties with swallowing.

Wherever they appear first signs of ALS, muscle weakness is gradually transferred to more and more parts of the body, although with the bulbar form of ALS, patients may not live to see complete paresis of the limbs due to respiratory arrest.

Over time, the patient loses the ability to move independently. ALS disease does not affect mental development, however, most often, deep depression begins - the person expects death. At the final stages of the disease, the muscles that perform the respiratory function are also affected, and the life of patients must be supported by artificial ventilation and artificial nutrition. It takes 3-5 years from observing the first signs of ALS to death. However, there are widely known cases where the condition of patients with clearly recognized ALS disease has stabilized over time.

WHO HAS BASS?

There are more than 350,000 ALS patients worldwide.

• per year, 5-7 people per 100,000 population are diagnosed with ALS. More than 5,600 Americans are diagnosed with ALS each year. That's 15 new cases of Bass per day
• ALS can affect anyone. Incidence rate (number of new ones) of ALS - 100,000 people per year
• Less than 10% of ALS cases are hereditary ALS can affect both men and women ALS affects all ethnic and socioeconomic groups
• ALS can affect young or very old adults, but is most often diagnosed in middle and late adulthood.
• People with ALS require expensive equipment, treatment and constant 24-hour care
• 90% of the burden of care falls on the shoulders of family members of people with ALS. ALS leads to a possible depletion of physical, emotional and financial resources. In Russia, there are more than 8,500 people with ALS; in Moscow, there are more than 600 people with ALS, although this number is officially underestimated. The most famous Russians who fell ill with ALS are Dmitry Shostakovich, Vladimir Migulya.

The causes of the disease are unknown. There is no cure for ALS. There was a slowdown in the progression of the disease. Life extension is possible with the help of a home ventilator.

Amyotrophic lateral sclerosis (Charcot's disease (Gehrig's disease) is a responsible diagnosis, tantamount to a medical “sentence.”

This diagnosis is not always simple, since in recent years the range of diseases has noticeably expanded, the clinical manifestations of which may not be a disease, but amyotrophic lateral sclerosis syndrome. Therefore, the most important task is to distinguish Charcot disease from amyotrophic lateral sclerosis syndrome and clarify the etiology of the latter.

Amyotrophic lateral sclerosis - severe organic disease of unclear etiology, characterized by damage to the upper and lower motor neurons, a progressive course and inevitably ending in death.

ICD-10 code

G12.2 Motor neuron disease

Symptoms of amyotrophic lateral sclerosis

Symptoms of amyotrophic lateral sclerosis, according to this definition, are symptoms of lower motor neuron damage, including weakness, atrophy, cramps and fasciculations, and symptoms of damage to the corticospinal tract - spasticity and increased tendon reflexes with pathological reflexes in the absence of sensory impairment. The corticobulbar tracts may be involved, exacerbating already established disease at the level of the brainstem. Amyotrophic lateral sclerosis is a disease of adults and does not begin in people under 16 years of age.

The most important clinical marker of the initial stages of amyotrophic lateral sclerosis is asymmetric progressive muscle atrophy with hyperreflexia (as well as fasciculations and cramps). The disease can begin in any striated muscle. There are high (progressive pseudobulbar palsy), bulbar ("progressive bulbar palsy"), cervicothoracic and lumbosacral forms). Death is usually associated with respiratory muscle involvement after approximately 3 to 5 years.

Most common symptom Amyotrophic lateral sclerosis, which occurs in approximately 40% of cases, is a progressive weakness of the muscles of one upper limb, usually starting in the hand (starting with the proximal muscles reflects a more favorable variant of the disease). If the onset of the disease is associated with the appearance of weakness in the muscles of the hand, then the thenar muscles are usually involved in the form of weakness of adduction (adduction) and opposition thumb. This makes it difficult to grasp with the thumb and index finger and leads to impairment of fine motor control. The patient experiences difficulty picking up small objects and getting dressed (buttons). If the dominant hand is affected, there is progressive difficulty in writing, as well as in daily household activities.

In the typical course of the disease, there is steadily progressive involvement of other muscles of the same limb and then spread to the other arm before the lower limbs or bulbar muscles are affected. The disease can also begin from the muscles of the face or mouth and tongue, from the muscles of the trunk (extensors suffer more than flexors) or lower extremities. At the same time, the involvement of new muscles never “catch up” with those muscles from which the disease began. Therefore, the shortest life expectancy is observed in the bulbar form: patients die from bulbar disorders while remaining on their feet (patients do not have time to live to see paralysis in the legs). A relatively favorable form is lumbosacral.

In the bulbar form, one or another combination of symptoms of bulbar and pseudobulbar palsy is observed, which is manifested mainly by dysarthria and dysphagia, and then by respiratory disorders. A characteristic symptom of almost all forms of amyotrophic lateral sclerosis is an early increase in the mandibular reflex. Dysphagia with liquids is more common than with solids, although swallowing solids becomes more difficult as the disease progresses. Weakness of the masticatory muscles develops, the soft palate hangs down, the tongue in the oral cavity is motionless and atrophic. Anarthria, continuous flow of saliva, and inability to swallow are observed. The risk of aspiration pneumonia increases. It is also useful to remember that cramps (often generalized) are observed in all patients with ALS and are often the first symptom of the disease.

It is characteristic that atrophies throughout the course of the disease are clearly selective. In the arms, the thenar, hypothenar, interosseous, and deltoid muscles are affected; on the legs - muscles that dorsiflex the foot; in the bulbar muscles - the muscles of the tongue and soft palate.

The extraocular muscles are the most resistant to damage in amyotrophic lateral sclerosis. Sphincter disorders are considered rare in this disease. Another intriguing feature of amyotrophic lateral sclerosis is the absence of pressure ulcers, even in patients who are paralyzed and bedridden (immobilized) for a long time. It is also known that dementia is rare in amyotrophic lateral sclerosis (with the exception of some subgroups: the familial form and the parkinsonism-ALS-dementia complex on the island of Guam).

Forms have been described with uniform involvement of the upper and lower motor neurons, with a predominance of damage to the upper (pyramidal syndrome with “primary lateral sclerosis") or lower (anterohorn syndrome) motor neuron.

Among paraclinical studies, electroneuromyography has the most significant diagnostic value. A widespread lesion of the cells of the anterior horns is revealed (even in clinically intact muscles) with fibrillations, fasciculations, positive waves, changes in motor unit potentials (their amplitude and duration increases) at a normal speed of excitation along the sensory nerve fibers. Plasma CPK levels may be slightly increased.

Diagnosis of amyotrophic lateral sclerosis

Diagnostic criteria for amyotrophic lateral sclerosis (according to Swash M., Leigh P 1992)

For the diagnosis of amyotrophic lateral sclerosis, the presence of:

• lower motor neuron symptoms (including EMG confirmation in clinically spared muscles)
• symptoms of upper motor neuron damage progressive course.

Criteria for excluding amyotrophic lateral sclerosis (negative diagnostic criteria)

The diagnosis of amyotrophic lateral sclerosis requires the absence of:

• sensory disorders
• sphincter disorders
• visual impairment
• autonomic disorders
• Parkinson's disease
• Alzheimer's type dementia
• ALS-mimicking syndromes.

Criteria for confirming amyotrophic lateral sclerosis

The diagnosis of amyotrophic lateral sclerosis is confirmed:

Fasciculations in one or more areas - EMG signs of neuronopathy; normal speed of excitation conduction along motor and sensory fibers (distal motor latencies may be increased); absence of conduction block.

Diagnostic categories for amyotrophic lateral sclerosis

Definite amyotrophic lateral sclerosis: presence of lower motor neuron symptoms plus upper motor neuron symptoms in 3 regions of the body.

Probable amyotrophic lateral sclerosis: lower motor neuron symptoms plus upper motor neuron symptoms in 2 regions of the body with upper motor neuron symptoms rostral to lower motor neuron symptoms.

Possible amyotrophic lateral sclerosis: lower motor neuron symptoms plus upper motor neuron symptoms in 1 body region or upper motor neuron symptoms in 2 or 3 body regions such as monomelic amyotrophic lateral sclerosis(manifestations of amyotrophic lateral sclerosis in one limb), progressive bulbar palsy and primary lateral sclerosis.

Suspicion of amyotrophic lateral sclerosis: lower motor neuron symptoms in 2 or 3 regions such as progressive muscle atrophy or other motor symptoms.

To clarify the diagnosis and carry out a differential diagnosis for amyotrophic lateral sclerosis, the following examination of the patient is recommended:

• Blood test (ESR, hematological and biochemical blood test);
• Chest X-ray;
• Thyroid function test;
• Determination of vitamin B12 and folic acid levels in the blood;
• Serum creatine kinase;
• MRI of the brain and, if necessary, the spinal cord;
• Lumbar puncture.

1. Spinal cord lesions:
   1. Cervical myelopathy.
   2. Other myelopathies (radiation, vacuolar in AIDS, electrical trauma).
   3. Ventral spinal cord tumor.
   4. Syringomyelia (anterior horn form).
   5. Subacute combined degeneration of the spinal cord (vitamin B12 deficiency).
   6. Familial spastic paraparesis.
   7. Progressive spinal amyotrophy (bulbospinal and other forms).
   8. Post-polio syndrome.
2. Lymphogranulomatosis and malignant lymphomas.
3. Gangliosidosis GM2.
4. Intoxication with heavy metals (lead and mercury).
5. ALS syndrome with paraproteinemia.
6. Creutzfeldt-Jakob disease.
7. Multifocal motor neuropathy.
8. Axonal neuropathy in Lyme disease.
9. Endocrinopathies.
10. Malabsorption syndrome.
11. Benign fasciculations.
12. Neuroinfections.
13. Primary lateral sclerosis.

Spinal cord lesions

Cervical myelopathy among others neurological manifestations often reveals typical symptoms of amyotrophic lateral sclerosis with hypotrophies (usually in the arms), fasciculations, tendon hyperreflexia and spasticity (usually in the legs). Amyotrophic lateral sclerosis syndrome in the picture of spondylogenic cervical myelopathy has a relatively favorable course and prognosis.

Diagnosis confirmed by the identification of other neurological manifestations of cervical myelopathy (including posterior column sensory disorders and sometimes dysfunction Bladder) and neuroimaging studies cervical spine spine and spinal cord.

Some other myelopathies (radiation myelopathy, vacuolar myelopathy due to HIV infection, consequences of electrical trauma) can also manifest themselves with the same or similar amyotrophic lateral sclerosis syndrome.

A ventral spinal cord tumor at the cervicothoracic level can manifest itself at certain stages with purely motor symptoms reminiscent of the cervicothoracic form of amyotrophic lateral sclerosis. Therefore, patients with spastic-paretic atrophies in the arms and spastic paraparesis in the legs always need a thorough examination to exclude compression damage to the spinal cord at the cervical and cervicothoracic levels.

Syringomyelia (especially its anterior horn form) at this level of the spinal cord can manifest a similar clinical picture. The identification of sensory disorders and neuroimaging examination are crucial in its recognition.

Subacute combined degeneration of the spinal cord with deficiency of vitamin B12 or folic acid (funicular myelosis) usually develops against the background of somatogenic malabsorption syndromes and is manifested in typical cases by symptoms of damage to the posterior and lateral columns of the spinal cord at the cervical and thoracic levels. The presence of lower spastic paraparesis with pathological reflexes in the absence of tendon reflexes sometimes forces this disease to be differentiated from amyotrophic lateral sclerosis. The diagnosis is helped by the presence of sensory disorders (impaired deep and superficial sensitivity), ataxia, and sometimes pelvic disorders, as well as the identification of a somatic disease (anemia, gastritis, condition of the tongue, etc.). Crucial in diagnosis is the study of the level of vitamin B12 and folic acid in the blood.

Strumpel's familial spastic paraparesis (paraplegia) refers to hereditary diseases upper motor neuron. Since there are forms of amyotrophic lateral sclerosis with predominant damage to the upper motor neuron, the differential diagnosis between them sometimes becomes very relevant. In addition, there is a rare variant of this disease (“hereditary spastic paraparesis with distal amyotrophy”), in which it is first necessary to exclude amyotrophic lateral sclerosis. The diagnosis is helped by a family history of Strumpel's disease and its more favorable course.

Progressive spinal amyotrophies

1. Bulbospinal, X-linked, Kennedy-Stephanie-Chukagosi amyotrophy is observed almost exclusively in men with the onset of the disease most often in the 2-3 decade of life and is manifested by fasciculations in the face (in the lower part), amyotrophic and paretic syndrome in the extremities (starting from the arm) and mild bulbar syndrome. Characterized by a family history, transient episodes of weakness and endocrine disorder syndrome (gynecomastia occurs in 50% of cases). Sometimes there is tremors and cramps. The course is benign (compared to amyotrophic lateral sclerosis).
2. The bulbar form of progressive spinal amyotrophy in children (Fazio-Londe disease) is inherited in an autosomal recessive manner, begins at the age of 1-12 years and is manifested by progressive bulbar palsy with the development of dysphagia, intense salivation, repeated respiratory infections and breathing disorders. General weight loss, decreased tendon reflexes, weakness of the facial muscles, and ophthalmoparesis may develop.
3. Differential diagnosis with amyotrophic lateral sclerosis may also require other forms of progressive spinal amyotrophy (proximal, distal, scapulo-peroneal, oculo-pharyngeal, etc.). Unlike amyotrophic lateral sclerosis, all forms of progressive spinal amyotrophy (PSA) are characterized by damage to only the lower motor neuron. All of them are manifested by progressive muscle atrophy and weakness. Fasciculations are not always present. There are no sensory disturbances. Sphincter functions are normal. In contrast to amyotrophic lateral sclerosis, already at the onset of PSA they manifest themselves as fairly symmetrical muscle atrophy and have a significant best forecast. Upper motor neuron (pyramidal sign) symptoms are never observed. An EMG study is crucial for diagnosis.

Post-polio syndrome

About a quarter of patients with residual paresis after poliomyelitis develop progressive weakness and atrophy of previously affected and previously unaffected muscles (post-polio syndrome) after 20-30 years. Weakness usually develops very slowly and does not reach a significant degree. The nature of this syndrome remains not entirely clear. In these cases, a differential diagnosis with amyotrophic lateral sclerosis may be necessary. The above criteria for diagnosing amyotrophic lateral syndrome are used.

Lymphogranulomatosis, as well as malignant lymphoma

These diseases can be complicated by paraneoplastic syndrome in the form of lower motor neuronopathy, which is not easy to differentiate from amyotrophic lateral sclerosis (but its course is still more benign with improvement in some patients). The predominant symptoms are lower motor neuron lesions with subacutely progressive weakness, atrophy and fasciculations in the absence of pain. Weakness is usually asymmetrical; The lower extremities are predominantly affected. When studying the conduction of excitation along the nerves, demyelination is noted in the form of a conduction block along the motor nerves. Weakness precedes lymphoma or vice versa.

Gangliosidosis GM2

Hexosaminidase type A deficiency in adults, which is phenomenologically distinct from the well-known Tay-Sachs disease in infants, can be accompanied by symptoms resembling motor neurone disease. Manifestations of hexosaminidase type A deficiency in adults are very polymorphic and can resemble both amyotrophic lateral sclerosis and progressive spinal amyotrophy. Another related genotype, which is based on hexosaminidase type A and B deficiency (Sendhoff disease), can also be accompanied by symptoms resembling motor neuron disease. Although amyotrophic lateral sclerosis syndrome appears to be the main manifestation of hexosaminidase-A deficiency in adults, the clinical spectrum of its manifestations still suggests that it is based on multisystem degeneration.

Intoxication with heavy metals (lead and mercury)

These intoxications (especially mercury) are now rare, but they can cause the development of amyotrophic lateral sclerosis syndrome with predominant damage to the lower motor neuron.

Amyotrophic lateral sclerosis syndrome with paraproteinemia

Paraproteinemia is a type of disproteinemia, which is characterized by the presence in the blood of a pathological protein (paraprotein) from the group of immunoglobulins. Paraproteinemias include multiple myeloma, Waldenström's macroglobulinemia, osteosclerotic myeloma (more often), primary amyloidosis, plasmacytoma and paraproteinemia of unknown origin. Some neurological complications in these diseases are based on the formation of antibodies to components of the myelin or axon. Polyneuropathy is most often observed (including in the picture of POEMS syndrome), less common cerebellar ataxia, Raynaud's phenomenon, but since 1968 amyotrophic lateral sclerosis syndrome (motor neuropathy) with weakness and fasciculations has also been periodically mentioned. Paraproteinemia has been described both in classic ALS and in a variant of amyotrophic lateral sclerosis syndrome with slow progression (in rare cases, immunosuppressive therapy and plasmapheresis led to some improvement in the condition).

Creutzfeldt-Jakob disease

Creutzfeldt-Jakob disease belongs to the group of prion diseases and typically begins at the age of 50-60 years; it has a subchronic course (most often 1-2 years) with a fatal outcome. Creutzfeldt-Jakob disease is characterized by a combination of dementia, extrapyramidal syndromes (akinetic-rigid, myoclonus, dystonia, tremor), as well as cerebellar, prohornal and pyramidal signs. Appears quite often epileptic seizures. For the diagnosis, importance is attached to the combination of dementia and myoclonus with typical changes on the EEG (triphasic and polyphasic activity acute form with an amplitude of up to 200 µV, occurring with a frequency of 1.5-2 per second) against the background of the normal composition of the cerebrospinal fluid.

Multifocal motor neuropathy

Multifocal motor neuropathy with conduction blocks occurs primarily in men and is clinically characterized by progressive asymmetric limb weakness with no or minimal sensory impairment. Weakness is usually (90%) distal and more severe in the arms than the legs. Muscle weakness in its distribution is often asymmetrically “tied” to individual nerves: the radial (“dangling hand”), ulnar and median. Atrophies are often detected, but may be absent in the early stages. Fasciculations and cramps are observed in almost 75% of cases; sometimes - myokymia. In approximately 50% of cases, tendon reflexes are reduced. But occasionally the reflexes remain normal and even accentuated, which gives reason to differentiate multifocal motor neuropathy from ALS. An electrophysiological marker is the presence of multifocal partial blocks of excitation conduction (demyelination).

Axonal neuropathy in Lyme disease

Lyme disease (Lyme borreliosis) is caused by a spirochete that enters the human body through a tick bite, and is a multisystem infectious disease that most often affects the skin (erythema migrans), the nervous system (aseptic meningitis; neuropathy). facial nerve, often bilateral; polyneuropathy), joints (recurrent mono- and polyarthritis) and heart (myocarditis, atrioventricular block and other heart rhythm disturbances). Subacute polyneuropathy in Lyme disease sometimes has to be differentiated from Guillain-Barré syndrome (especially in the presence of diplegia facialis). However, patients with polyneuropathy due to Lyme disease almost always exhibit pleocytosis in the cerebrospinal fluid. Some patients with borreliosis develop primarily motor polyradiculitis, which may resemble motor neuronopathy with symptoms similar to ALS. CSF examination can again help in the differential diagnosis.

Endocrinopathies

Hypoglycemia associated with hyperinsulinism is one of the known endocrinopathies described in foreign and domestic literature that can lead to the development of amyotrophic lateral sclerosis syndrome. Another form of endocrinopathy - thyrotoxicosis - can resemble amyotrophic lateral sclerosis with pronounced general weight loss and the presence of symmetrically high tendon reflexes (sometimes Babinski's sign and fasciculations occur), which is often observed with untreated thyrotoxicosis. Hyperparathyroidism is most often caused by an adenoma parathyroid gland and leads to disturbances in the metabolism of calcium (hypercalcemia) and phosphorus. Complications from the nervous system concern either mental functions (memory loss, depression, less commonly - psychotic disorders), or (less often) - motor. In the latter case, muscle atrophy and weakness sometimes develop, usually more noticeable in proximal parts legs and often accompanied by pain, hyperreflexia and fasciculations in the tongue; Dysbasia develops, sometimes resembling a duck gait. Safe or increased reflexes against the background of muscle atrophy sometimes serve as a basis for suspicion of amyotrophic lateral sclerosis. Finally, in practical work there are sometimes cases of diabetic “amyotrophy” that require a differential diagnosis with ALS. In the diagnosis of movement disorders in endocrinopathies, it is important to recognize endocrine disorders and apply diagnostic (and exclusion) criteria for amyotrophic lateral sclerosis.

Malabsorption syndrome

Severe malabsorption is accompanied by impaired metabolism of vitamins, electrolytes, anemia, various endocrine and metabolic disorders, which sometimes leads to severe neurological disorders in the form of encephalopathy (usually with brainstem, cerebellar and other manifestations) and damage to the peripheral nervous system. Among the neurological manifestations of severe malabsorption, a rare syndrome is a symptom complex reminiscent of amyotrophic lateral sclerosis.

Benign fasciculations

The presence of fasciculations alone without EMG signs of denervation is insufficient for the diagnosis of ALS. Benign fasciculations continue for years without any signs of involvement motor system(there is no weakness, atrophy, relaxation time does not change, reflexes do not change, the speed of excitation along the nerves does not change; there are no sensory disorders; muscle enzymes remain normal). If for some reason there is a general loss of weight in the patient, then sometimes in such cases there is a reasonable suspicion of ALS.

Neuroinfections

Some infectious lesions nervous system (poliomyelitis (rare), brucellosis, epidemic encephalitis, tick-borne encephalitis, neurosyphilis, HIV infection, the above-mentioned Lyme disease, “Chinese paralytic syndrome”) may be accompanied by a variety of neurological syndromes, including pyramidal and prohornal symptoms, which may certain stages of the disease raise suspicion of ALS syndrome.

Primary lateral sclerosis

Primary lateral sclerosis is an extremely rare disease in adulthood and old age, which is characterized by progressive spastic tetraparesis preceding or following pseudobulbar dysarthria and dysphagia, reflecting the combined involvement of the corticospinal and corticobulbar tracts. There are no fasciculations, atrophies or sensory disturbances. EMG and muscle biopsy show no evidence of denervation. Although long survival has been described among patients with primary lateral sclerosis, there are patients with the same fast current, which is typical for ALS. The final nosological affiliation of this disease has not been established. The prevailing view is that primary lateral sclerosis is an extreme variant of ALS, when the disease is limited to damage to only the upper motor neuron.

In the literature one can find isolated descriptions of syndromes reminiscent of amyotrophic lateral sclerosis in diseases such as radiation damage to the nervous system (motor neuropathy), myositis with inclusion bodies, paraneoplastic encephalomyelitis involving cells of the anterior horns, juvenile spinal muscular atrophy with distal atrophies in the arms, the disease Machado-Joseph, multiple system atrophy, Hallervorden-Spatz disease, some tunnel neuropathies, craniovertebral junction abnormalities.

AMYOTROPHIC LATERAL SCLEROSIS (ALS, “Charcot’s disease”, “Gehrig’s disease”, “motor neuron disease”) is an idiopathic neurodegenerative progressive disease of unknown etiology, caused by selective damage to peripheral motor neurons of the anterior horns of the spinal cord and motor nuclei of the brain stem, as well as cortical (central) motor neurons and lateral columns of the spinal cord.

Despite more than 100 years of study, amyotrophic lateral sclerosis (ALS) remains a fatal disease of the central nervous system. The disease is characterized by a steadily progressive course with selective damage to the upper and lower motor neurons, which leads to the development of amyotrophy, paralysis and spasticity. To date, questions of etiology and pathogenesis remain unclear, and therefore specific methods for diagnosing and treating this disease have not been developed. A number of authors have noted an increase in the incidence of the disease among individuals young(up to 40 years old).

ICD-10 G12.2 Motor neuron disease

EPIDEMIOLOGY

Amyotrophic lateral sclerosis debuts between 40 and 60 years of age. Average age onset of the disease at 56 years of age. ALS is a disease of adults, and is not observed in persons under 16 years of age. Men are slightly more likely to get sick(male-female ratio 1.6-3.0:1).

ALS is sporadic disease and occurs with a frequency of 1.5 - 5 cases per 100,000 population.
IN 90% of ALS cases are sporadic, and in 10% - family or hereditary nature like with autosomal dominant(mostly) and with autosomal recessive types of inheritance. The clinical and pathological characteristics of familial and sporadic ALS are almost identical.

Currently age is the main risk factor with ALS, which is confirmed by an increase in incidence after 55 years, and in this age group there are no longer differences between men and women. Despite the reliable connection between ALS and age, aging is only one of the predisposing factors in the development of the pathological process. The variability of the disease both in different age groups and among people of the same age suggests the existence of certain risk factors: deficiency, or vice versa, the presence of certain neuroprotective factors, which currently include: neurosteroids or sex hormones; neurotrophic factors; antioxidants.

Some researchers note a particularly favorable course of the disease in young women, which confirms the undoubted role of sex hormones, especially estradiol and progestin, in the pathogenesis of amyotrophic lateral sclerosis. This is confirmed by: the high incidence of ALS in men under 55 years of age (they have an earlier onset and rapid progression of the disease compared to women); with the onset of menopause, women get sick as often as men; isolated cases of amyotrophic lateral sclerosis during pregnancy. To date, there are only a few studies on the hormonal status of patients with amyotrophic lateral sclerosis, and not a single one devoted to determining hormone concentrations in young patients.

ETIOLOGY

The etiology of the disease is not clear. The role of viruses, immunological and metabolic disorders is discussed.

The role of mutation in the gene has been shown in the development of familial ALS superoxide dismutase-1(Cu/Zn-superoxide dismutase, SOD1), chromosome 21q22-1, ALS associated with chromosome 2q33-q35 was also detected.

Syndromes that are clinically indistinguishable from classic ALS may result from:
Structural lesions:
parasagittal tumors
tumors of the foramen magnum
spondylosis of the cervical spine
Arnold-Chiari syndrome
hydromyelia
arteriovenous anomaly of the spinal cord
Infections:
bacterial - tetanus, Lyme disease
viral - polio, herpes zoster
retroviral myelopathy
Intoxications, physical agents:
toxins - lead, aluminum, other metals.
medications - strychnine, phenytoin
electric shock
x-ray radiation
Immunological mechanisms:
plasma cell dyscrasia
autoimmune polyradiculoneuropathy
Paraneoplastic processes:
paracarcinomatous
paralymphomatous
Metabolic disorders:
hypoglycemia
hyperparathyroidism
thyrotoxicosis
folic acid deficiency,
vitamins B12, E
malabsorption
Hereditary biochemical disorders:
androgen receptor defect - Kennedy's disease
hexosaminidase deficiency
a-glucosidase deficiency - Pompe disease
hyperlipidemia
hyperglycinuria
methylcrotonylglycinuria

All of these conditions can cause the symptoms found in ALS and should be considered in the differential diagnosis.

PATHOGENESIS

Today there is no generally accepted hypothesis for the pathogenesis of amyotrophic lateral sclerosis. According to modern ideas, the development of ALS is caused by the interaction of hereditary and exogenous provoking factors. Many pathological changes in neurons lead to the assumption of a multivariate etiological factor.

Disorders at the cellular level in motor neuron disease are extensive and include:
changes in the cytoskeleton: structural disorganization of neurofilaments, which leads to disruption of axonal transport
toxic effect of intracellular protein aggregates affecting the functioning of the mitochondrial apparatus and disruption of the secondary assembly of cytoplasmic proteins
microglial activation and changes in free radical and glutamate metabolism.

Normally, SOD-1 inhibits IL-1b-converting enzyme. Under the influence of the latter, IL-1b is formed, which initiates the death of neurons after binding to its membrane receptor. The product of the defective SOD-1 gene is not capable of inhibiting the IL-1b-converting enzyme; the resulting IL-b induces the death of motor neurons at various levels of the nervous system.

Current views on the pathogenesis of amyotrophic lateral sclerosis include understanding of the major role of oxidative stress in the development of this pathology.

Supposed that hydrogen peroxide may serve as an anomalous substrate for the conformed SOD1 molecule. As a result, peroxidant reactions intensify and the production of toxic hydroxyl radicals increases. The significant role of oxidative stress in the pathogenesis of ALS is confirmed by biochemical studies, which revealed the presence of insufficiency of a number of systems in patients antioxidant protection, mitochondrial dysfunction, glutathione dysmetabolism, glutamate excitotoxin and glutamate transport mechanisms. Perhaps oxidative damage to protein targets (SOD1, neurofilament proteins, alpha-synuclen, etc.) can facilitate and accelerate their joint aggregation and the formation of cytoplasmic inclusions, which serve as a substrate for further pathochemical oxidative reactions.

CLASSIFICATION

Based on the predominant localization of damage to various muscle groups, the following forms of amyotrophic lateral sclerosis are distinguished:
cervicothoracic form(50% of cases)
bulbar form(25% of cases)
lumbosacral shape(20 – 25% of cases)
high (cerebral) form(1 – 2%)

A separate variant of ALS includes the “ALS-plus” syndromes, which include:
ALS combined with frontotemporal dementia. It is most often familial in nature and accounts for 5-10% of cases of the disease.
ALS, combined with frontal dementia and parkinsonism, and associated with a mutation of the 17th chromosome.

North American Classification of ALS (Hudson A.J. 1990)
Sporadic ALS
1. Classic ALS
Debuts:
bulbar
cervical
chest
lumbar
diffuse
respiratory
2. Progressive bulbar palsy
3. Progressive muscular atrophy
4. Primary lateral sclerosis
Familial ALS
1. Autosomal dominant

without SOD-1 mutation (mutations of other genes, genetic defect unknown)
2. Autosomal recessive
associated with SOD-1 mutations
other forms (a total of 10 linkage loci are known)
3. Western Pacific ALS-parkinsonism-dementia complex

Classification of ALS O.A. Khondkariana (1978)
Forms of ALS:
bulbar
cervicothoracic
lumbosacral
primary generalized
high
Options:
mixed (classic)– uniform damage to the central nervous system and the central nervous system
segmental-nuclear– predominant lesion of PMN
pyramidal (high form of ALS)– predominant lesion of CMN

PATHOMORPHOLOGY

During pathomorphological examination they find:
selective atrophy of the anterior motor roots and cells of the anterior horns of the spinal cord, the most pronounced changes occur in the cervical and lumbar segments
the posterior sensory roots remain normal
V nerve fibers of the lateral corticospinal tracts of the spinal cord, demyelination, uneven swelling is observed, followed by disintegration and death of the axial cylinders, which usually extends to the peripheral nerves
in some cases, atrophy of the precerebral gyrus of the cerebrum is noted, sometimes atrophy affects the VIII, X and XII pairs of cranial nerves, the most pronounced changes occur in the nucleus of the hypoglossal nerve
atrophy or absence of motor neurons, accompanied by moderate gliosis without signs of inflammation
loss of giant pyramidal cells (Betz cells) of the motor cortex
degeneration of the lateral pyramidal tract of the spinal cord
atrophy of muscle fiber groups (as part of motor units)

CLINIC

Initial manifestations of the disease:
weakness in the distal parts of the arms, clumsiness with fine movements of the fingers, thinning of the hands and fasciculations (muscle twitching)
less commonly, the disease debuts with weakness in the proximal arms and shoulder girdle, atrophy in the leg muscles in combination with lower spastic paraparesis
It is also possible that the disease begins with bulbar disorders - dysarthria and dysphagia (25% of cases)
cramps (painful contractions, muscle spasms), often generalized, occur in almost all patients with ALS, and are often the first sign of the disease

Characteristic clinical manifestations of ALS
Amyotrophic lateral sclerosis is characterized by combined damage to the lower motor neuron (peripheral) and damage to the upper motor neuron (pyramid tract and/or pyramidal cells of the motor cortex of the brain.
Signs of lower motor neuron damage:
muscle weakness (paresis)
hyporeflexia (decreased reflexes)
muscle atrophy
fasciculations (spontaneous, rapid, irregular contractions of muscle fiber bundles)
Signs of upper motor neuron damage:
muscle weakness (paresis).
spasticity (increased muscle tone)
hyperreflexia (increased reflexes)
pathological foot and hand signs

For ALS in most cases characterized by asymmetry of symptoms.

In atrophied or even apparently intact muscles, they are found fasciculations(muscle twitching), which can appear in a local muscle group or be widespread.

In a typical case, the onset of the disease is with loss of thenar muscles one of the hands with the development of weakness of adduction (adduction) and opposition of the thumb, (usually asymmetrically), which makes it difficult to grasp with the thumb and index finger and leads to disturbances in fine motor control in the muscles of the hand. The patient experiences difficulty picking up small objects, fastening buttons, and writing.

Then, as the disease progresses, the muscles of the forearm are involved in the process, and the hand takes on the appearance of a “clawed paw”. A few months later, a similar lesion develops on the other arm. Atrophy, gradually spreading, affects the muscles of the shoulder and shoulder girdle.

At the same time or later Damage to the bulbar muscles often develops: fasciculations and atrophy of the tongue, paresis soft palate, atrophy of the muscles of the larynx and pharynx, which manifests itself in the form of dysarthria (speech problems), dysphagia (swallowing problems), and drooling.

The muscles of facial expression and mastication are usually affected later than other muscle groups. As the disease progresses, it becomes impossible to stick out the tongue, puff out the cheeks, or pull the lips into a tube.

Sometimes weakness of the extensors of the head develops, due to which the patient cannot hold his head straight.

When the diaphragm is involved in the process Paradoxical breathing is observed (the stomach sinks in when inhaling, and protrudes when exhaling).

The legs are usually the first to atrophy anterior and lateral muscle groups, which is manifested by a “dropping foot” and a steppage-type gait (the patient raises his leg high and throws it forward, sharply lowering it).

!!! It is characteristic that muscle atrophy is selective.
Atrophy is observed on the hands:
tenara
hypothenar
interosseous muscles
deltoid muscles
Muscles in the legs are involved performing dorsiflexion of the foot.
In the bulbar muscles The muscles of the tongue and soft palate are affected.

Pyramid syndrome usually develops on early stage ALS is manifested by revitalization of tendon reflexes. Following this, lower spastic paraparesis often develops. In the hands, increased reflexes are combined with muscle atrophy, i.e. combined, simultaneous damage to the central (pyramidal) pathways and peripheral motor neurons is observed, which is characteristic of ALS. Superficial abdominal reflexes disappear as the process progresses. Babinski's symptom (when the sole of the foot is irritated with streaks, the big toe extends, the other toes fan out and extend) is observed in half of the cases of the disease.

There may be sensory disturbances. In 10% of patients, paresthesia is observed in the distal parts of the arms and legs. The pain, sometimes severe, usually at night, can be associated with joint stiffness, prolonged immobility, spasms due to high spasticity, cramps (painful muscle spasms), and depression. Loss of sensitivity is not typical.

Oculomotor disorders are not typical and are found on terminal stages diseases.

!!! Disorders of the pelvic organs are not typical, but in an advanced stage, urinary retention or incontinence may occur.

Moderate cognitive impairment(decreased memory and mental performance) occur in half of the patients. 5% of patients develop frontal-type dementia, which can be combined with parkinsonian syndrome.

!!! A feature of ALS is the absence of bedsores even in paralyzed bedridden patients.

Clinic of the main forms of the disease
Cervicothoracic form(50% of cases):
characterized by atrophic and spastic-atrophic paresis of the arms and spastic paresis of the legs
Bulbar form:
occurs in 25% of ALS cases
bulbar disorders predominate (paralysis of the soft palate, tongue, weakness of the masticatory muscles, speech disorders, swallowing, continuous flow of saliva, late stages respiratory disorders), possible addition of pseudobulbar manifestations in the form of violent laughter and crying, revitalization of the mandibular reflex
later signs of damage to the limbs appear
this form has the shortest life expectancy: patients die from bulbar disorders (due to aspiration pneumonia, respiratory failure), while often remaining capable of independent movement
Lumbosacral form(20 – 25% of cases):
atrophic paresis of the legs develops with mild pyramidal symptoms
in later stages, the muscles of the arms and cranial muscles are involved
High (cerebral) form(1 – 2%):
manifested by spastic tetraparesis (or lower paraparesis), pseudobulbar syndrome (violent laughter and crying, revitalization of the mandibular reflex) with minimal signs of damage to peripheral motor neurons

Complications of ALS
paresis and paralysis of the limbs, neck muscles (inability to hold the head up)
swallowing disorders
breathing disorders, respiratory failure
aspiration pneumonia
limb contractures
urosepsis
depression
multiple cramps (painful muscle spasms)
cachexia

Progression of movement disorders ends in death in a few (2-6) years. Sometimes the disease has an acute course.

DIAGNOSTICS

Diagnosis of amyotrophic lateral sclerosis primarily based on thorough analysis of the clinical picture of the disease. An EMG study (electromyography) confirms the diagnosis of motor neuron disease.

Amyotrophic lateral sclerosis should be suspected:
with the development of weakness and atrophy, and possibly fasciculations (muscle twitching) in the muscles of the hand
with loss of weight in the thenar muscles of one of the hands with the development of weakness of adduction (adduction) and opposition of the thumb (usually asymmetrical)
in this case, there is difficulty in grasping with the thumb and forefinger, difficulty in picking up small objects, when fastening buttons, when writing
with the development of weakness in the proximal arms and shoulder girdle, atrophy in the leg muscles in combination with lower spastic paraparesis
if the patient develops dysarthria (speech problems) and dysphagia (swallowing problems)
when the patient experiences cramps (painful muscle contractions)

Diagnostic criteria for ALS of the World Organization of Neurologists (1998):
damage (degeneration) of the lower motor neuron, proven clinically, electrophysiologically or morphologically
damage (degeneration) of the upper motor neuron according to the clinical picture
the progressive development of subjective and objective signs of the disease at one level of damage to the central nervous system or their spread to other levels, determined by anamnesis or examination

!!! In this case, it is necessary to exclude other possible causes of degeneration of the lower and upper motor neurons.

Diagnostic criteria for ALS:
Clinically definite ALS is diagnosed:
in the presence of clinical signs of damage to the upper motor neuron (for example, spastic paraparesis) and lower motor neuron at the bulbar and at least two spinal levels (damage to the arms, legs)
or
in the presence of clinical signs of upper motor neuron damage at two spinal levels and lower motor neuron damage at three spinal levels
Clinically probable ALS is diagnosed:
with damage to the upper and lower motor neurons at at least two levels of the central nervous system
And
in the presence of symptoms of upper motor neuron damage above the levels of lower motor neuron damage
Clinically possible ALS:
lower motor neuron symptoms plus upper motor neuron symptoms in 1 region of the body
or
upper motor neuron symptoms in 2 or 3 regions of the body, such as monomelic ALS (manifestations of ALS in one limb), progressive bulbar palsy
Suspicion of ALS:
if you have lower motor neuron symptoms in 2 or 3 regions, such as progressive muscle atrophy or other motor symptoms

NB!!! Regions of the body are divided into:
oral-facial
brachial
crural
thoracic
trunk

Criteria for confirming ALS:
fasciculations in one or more areas
combination of signs of bulbar and pseudobulbar palsy
rapid progression to death within several years
absence of oculomotor, pelvic, visual disturbances, loss of sensitivity
non-myotomic distribution of muscle weakness (eg, simultaneous development of weakness in the biceps brachii and deltoid muscles; both are innervated by the same spinal segment, although by different motor nerves)
no signs of simultaneous damage to the upper and lower motor neurons in the same spinal segment
non-regional distribution of muscle weakness (for example, if paresis first develops in the right arm, the right leg is usually further involved in the process or left hand, but not the left leg)
unusual course of the disease over time (ALS is not characterized by onset before 35 years of age, duration of more than 5 years, absence of bulbar disorders after one year of illness, indications of remission)

ALS exclusion criteria
To diagnose amyotrophic lateral sclerosis, the absence of:
sensory disorders, primarily loss of sensitivity (possible paresthesia and pain)
pelvic disorders - disorders of urination and defecation (their addition is possible at the final stages of the disease)
visual impairment
autonomic disorders
Parkinson's disease
Alzheimer's type dementia
ALS-like syndromes

EMG(electromyography) helps in confirming clinical data and findings.
Characteristic changes and EMG findings in ALS:
fibrillation and fasciculations in the muscles of the upper and lower extremities, or in the extremities and head area
decrease in the number of motor units and increase in the amplitude and duration of the motor unit action potential
normal conduction velocity in the nerves innervating slightly affected muscles, and decreased conduction velocity in the nerves innervating severely affected muscles (velocity should be at least 70% of the normal value)
normal electrical excitability and impulse conduction speed along the fibers of sensory nerves

Differential diagnosis ALS (ALS-like syndromes):
Spondylogenic cervical myelopathy.
Tumors of the craniovertebral region and spinal cord.
Craniovertebral anomalies.
Syringomyelia.
Subacute combined degeneration of the spinal cord with vitamin B12 deficiency.
Strumpel's familial spastic paraparesis.
Progressive spinal amyotrophies.
Post-polio syndrome.
Intoxication with lead, mercury, manganese.
Hexosaminidase type A deficiency in adults with GM2 gangliosidosis.
Diabetic amyotrophy.
Multifocal motor neuropathy with conduction blocks.
Creutztfeldt-Jakob disease.
Paraneoplastic syndrome, in particular with lymphogranulomatosis and malignant lymphoma.
ALS syndrome with paraproteinemia.
Axonal neuropathy in Lyme disease (Lyme borreliosis).
Radiation myopathy.
Guillain-Barre syndrome.
Myasthenia.
Multiple sclerosis.
ONMK.
Endocrinopathies (thyrotoxicosis, hyperparathyroidism, diabetic amyotrophy).
Malabsorption syndrome.
Benign fasciculations, i.e. fasciculations that continue for years without signs of damage to the motor system.
Neuroinfections (poliomyelitis, brucellosis, epidemic encephalitis, tick-borne encephalitis, neurosyphilis, Lyme disease).
Primary lateral sclerosis.

TREATMENT

There is no effective treatment for the disease. The only drug, the glutamate release inhibitor riluzole (Rilutek), delays death by 2 to 4 months. It is prescribed 50 mg twice a day.

The basis of treatment is symptomatic therapy:
Physiotherapy.
Physical activity. The patient should, to the best of his ability, support physical activity As the disease progresses, the need for a wheelchair and other special devices arises.
Diet. Dysphagia creates a risk of food entering the airways. Sometimes there is a need for feeding through a tube or gastrostomy.
Use of orthopedic devices: cervical collar, various tires, devices for grasping objects.
For cramps (painful muscle spasms): quinine sulfate 200 mg twice a day, or phenytoin (Difenin) 200–300 mg/day, or carbamazepine (Finlepsin, Tegretol,) 200–400 mg/day, and/or vitamin E 400 mg twice a day, as well as magnesium preparations, verapamil (Isoptin).
For spasticity: baclofen (Baclosan) 10 – 80 mg/day, or tizanidine (Sirdalud) 6 – 24 mg/day, as well as clonazepam 1 – 4 mg/day, or memantine 10 – 60 mg/day.
When drooling atropine 0.25 - 0.75 mg three times a day, or hyoscine (Buscopan) 10 mg three times a day.
If it is impossible to eat due to impaired swallowing, a gastrostomy tube is placed or a nasogastric tube is inserted. Early percutaneous endoscopic gastrostomy prolongs the life of patients by an average of 6 months.
For pain syndromes use the entire arsenal of analgesics. Including narcotic analgesics in the final stages.
Sometimes some temporary improvement bring anticholinesterase drugs (neostigmine methyl sulfate - prozerin).
Cerebrolysin in high doses(10-30 ml IV drip for 10 days in repeated courses). There are a number of small studies showing the neuroprotective efficacy of Cerebrolysin in ALS.
Antidepressants: Sertaline 50 mg/day or Paxil 20 mg/day or Amitriptyline 75-150 mg/day (the drug is cheaper, but has more pronounced side effects; some ALS patients prefer it precisely because side effects– it causes dry mouth, and accordingly reduces hypersalivation (salivation), which often plagues patients with ALS).
When breathing problems occur: artificial ventilation As a rule, lung ventilation is not performed in hospitals, but some patients purchase portable ventilators and perform mechanical ventilation at home.
Developments are underway for the use of growth hormone, neurotrophic factors in ALS.
Lately Stem cell treatment is being actively developed. This method promises to be promising, but is still at the stage of scientific experiments.

FORECAST

Amyotrophic lateral sclerosis is a fatal disease. Average duration The lifespan of patients with ALS is 3–5 years, however, 30% of patients live 5 years, and about 10–20% live more than 10 years from the onset of the disease.

Poor prognostic signs– elderly age and bulbar disorders (after the appearance of the latter, patients live no more than 1–3 years).

PREVENTION

There is no specific prevention.